Quality Control

Quality Control & MSDS

Chemical structure

Biological Activity

Description

BS-181 HCl is a highly selective inhibitor of CDK7 with an IC50 value of 21 nM.

Targets

CDK7

IC50

21 nM

Protocol

Kinase experiment [1]:

In vitro kinase inhibition.

Inhibition of CDK7 activity was measured by incubation of increasing amounts of BS-181 HCl with purified recombinant CDK7/CycH/MAT1 complex, followed by measurement of free ATP remaining in the reaction using a luciferase assay, luciferase activity therefore providing a measure of inhibition of CDK7 activity for the determination of IC50.

Cell experiment [1]:

Cell lines

MCF-7 cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

50 μM; 24 hrs

Applications

In MCF-7 cells, BS-181 HCl inhibited the phosphorylation of CDK7 substrates, and promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines.

Background

IC50: 21 nm (CDK7)

Normal progression through the cell cycle requires the sequential action of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6. Direct or indirect deregulation of CDK activity is a feature of almost all cancers and has led to the development of CDK inhibitors as anticancer agents.BS-181 is a highly selective CDK7 inhibitor with IC50 of 21 nM. ; >40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.

In vitro: BS-181, inhibited CAK activity with an IC50 of 21 nmol/L. Testing of other CDKs as well as another 69 kinases showed that BS-181 only inhibited CDK2 at concentrations lower than 1 μmol/L, with CDK2 being inhibited 35-fold less potently (IC50 880 nmol/L) than CDK7. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines [1].

In vivo: BS-181 was stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. The same dose of drug inhibited the growth of MCF-7 human xenografts in nude mice. BS-181 therefore provides the first example of a potent and selective CDK7 inhibitor with potential as an anticancer agent [1].

Clinical trial: BS-181 is currently in the preclinical development and non clinical trial is ongoing.